Safety and Efficacy of Umbilical Cord Blood Regulatory T Cells Plus Liraglutide on Autoimmune Diabetes

Type1 Diabetes Mellitus Clinical Trial

Official title:

Phase 1/ Phase 2 Study of the Therapeutic Effect of Ex-vivo Expanded Umbilical Cord Blood Regulatory T Cells With Liraglutide on Autoimmune Diabetes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03011021
• Other study ID #: 0001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 2017
• Est. completion date: June 2025

Study information

• Verified date: March 2023
• Source: Second Xiangya Hospital of Central South University
• Contact: Zhiguang Zhou, MD/PhD
• Phone: 86-731-85292154
• Email: zhouzg[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate the safety and therapeutic effect of ex-vivo expanded umbilical cord blood regulatory T cells adjunct with Liraglutide on autoimmune diabetes.

Description:

Autoimmune Diabetes Mellitus (AIDM) is a subtype of diabetes mellitus caused by autoimmune destruction of beta cells in the islet, including Type 1 diabetes and Latent Autoimmune Diabetes in Adults (LADA). Insulin has been used as a routine therapy for AIDM to alleviate the hyperglycemic status, yet cannot effectively prevent the progressing destruction of beta cells or preserve its function. Regulatory T cells expanded from umbilical cord blood (UCB-Treg) ex-vivo have shown strong capacity to control immune responses in autoimmune diseases, offering a hopeful therapeutic way for AIDM. Glucagon-like peptide (GLP-1) analog Liraglutide has been tested in large-scale clinical trial to prove its various benefits for beta cells and glucolipid metabolism in Type 2 diabetes and obesity patients. However, its clinical application in AIDM is not well-defined so far. The aim of this study is to investigate the potential use of Liraglutide with UCB-Treg infusion in AIDM and examine the safety and efficacy of this new therapy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: June 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Type 1 diabetes according to ADA criteria <3 years.
• Age= 18 years.
• Positive for at least one of the anti-islet autoantibodies: GADA, IA2A, ZnT8A
• Fasting or postprandial plasma C-peptide more than 100 pmol/L
• Written informed consent from the patient or family representative.

Exclusion Criteria:

• History or family history of medullary thyroid carcinoma or MEN 2 syndrome;
• History of chronic or acute pancreatitis;
• Allergic to liraglutide or any components in Victoza®;
• Hepatic abnormalities (transaminase > 2 times normal);
• Renal impairments (serum creatinine >133 umol/L);
• Cardiovascular diseases (hypertension, coronary heart disease, etc.);
• Presence of anemia (Hb =100g/L), leukopenia (<3.5×109/L);
• Presence of disorder in coagulation or anticoagulation, or thrombocytopenia (platelets <100×109/L);
• Presence of acute metabolic disorders; In the case of acute ketone acidosis, with blood ketone over 0.3mmol/L and pH lower than 7.30;
• Presence of any kind of chronic infection or immune deficiency, including hepatitis B, hepatitis C, HIV, syphilis or tuberculosis, etc.;
• Chronic use of systemic glucocorticoids or other immunosuppressive agents for over 3 months;
• Any history of malignancy;
• Female patients who are pregnant or breastfeeding; any female who is unwilling to use a reliable and effective form of contraception for 2 years after recruitment;
• Presence of any infectious diseases, including active skin infections, flu, fever, upper or lower respiratory tract infections; those who wish to participate in the study should keep the infection under control for at least 1 week before receiving Treg product infusion;
• Any medical condition that, in the opinion of the investigator, will interfere with safe participation in the trial.

Related Conditions & MeSH terms

• Autoimmune Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type1 Diabetes Mellitus

Intervention

Drug:
• Liraglutide
Dose escalation of Liraglutide starts from 0.6 mg up to 1.2 mg per day.

Biological:
• UCB-Treg
Receive Treg infusion: 1~5*10^6/kg b.w. in 100ml normal saline

Drug:
• Insulin
Receive insulin following clinician's instruction.

Locations

Country	Name	City	State
China	Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University	Changsha	Hunan

Sponsors (1)

Lead Sponsor	Collaborator
Second Xiangya Hospital of Central South University

Country where clinical trial is conducted

China, 

References & Publications (6)

Brunstein CG, Miller JS, Cao Q, McKenna DH, Hippen KL, Curtsinger J, Defor T, Levine BL, June CH, Rubinstein P, McGlave PB, Blazar BR, Wagner JE. Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: safety profile and detection kinetics. Blood. 2011 Jan 20;117(3):1061-70. doi: 10.1182/blood-2010-07-293795. Epub 2010 Oct 15. — View Citation

Chang TJ, Tseng HC, Liu MW, Chang YC, Hsieh ML, Chuang LM. Glucagon-like peptide-1 prevents methylglyoxal-induced apoptosis of beta cells through improving mitochondrial function and suppressing prolonged AMPK activation. Sci Rep. 2016 Mar 21;6:23403. doi: 10.1038/srep23403. Erratum In: Sci Rep. 2016 May 31;6:26917. — View Citation

Fan H, Yang J, Hao J, Ren Y, Chen L, Li G, Xie R, Yang Y, Gao F, Liu M. Comparative study of regulatory T cells expanded ex vivo from cord blood and adult peripheral blood. Immunology. 2012 Jun;136(2):218-30. doi: 10.1111/j.1365-2567.2012.03573.x. — View Citation

Milward K, Issa F, Hester J, Figueroa-Tentori D, Madrigal A, Wood KJ. Multiple unit pooled umbilical cord blood is a viable source of therapeutic regulatory T cells. Transplantation. 2013 Jan 15;95(1):85-93. doi: 10.1097/TP.0b013e31827722ed. — View Citation

Rondas D, D'Hertog W, Overbergh L, Mathieu C. Glucagon-like peptide-1: modulator of beta-cell dysfunction and death. Diabetes Obes Metab. 2013 Sep;15 Suppl 3:185-92. doi: 10.1111/dom.12165. — View Citation

Zoso A, Serafini P, Lanzoni G, Peixoto E, Messinger S, Mantero A, Padilla-Tellez ND, Baidal DA, Alejandro R, Ricordi C, Inverardi L. G-CSF and Exenatide Might Be Associated with Increased Long-Term Survival of Allogeneic Pancreatic Islet Grafts. PLoS One. 2016 Jun 10;11(6):e0157245. doi: 10.1371/journal.pone.0157245. eCollection 2016. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse effects	Primary outcome measures will be the number of participants with adverse events, laboratory abnormalities and other signs of toxicity. Particular focus will be on the number and severity of infusion reactions, complications related to infection, and any potential negative impact on the course of diabetes.	2 years
Secondary	Change in HbA1C	Measure the HbA1C level after treatment	2 years
Secondary	Change in C-peptide	Measure the C-peptide level after treatment	2 years
Secondary	Change in insulin dose	Measure insulin dose patient used after treatment	2 years
Secondary	Hypoglycaemic events	Measure the number of participants with Hypoglycaemic events	2 years
Secondary	Change in titer of autoantibodies	Measure the titer of antoantibodies of participant after treatment	2 years
Secondary	Change in immune cells diversities and quantities.	Measure the immune cells diversities and quantities after treatment	2 years
Secondary	Change in autoimmune-related cytokines	Measure the change of autoimmune- related cytokines after treatment	2 years
Secondary	Life quality evaluation	Number of participants with disturbance of emotion, sleep, resting or energy.	2 years